The need for biomedical sensors and in particular glucose sensors for preventing hypo-glycemic and hyperglycemic events in diabetics and for closed-loop controlling the insulin infusion via a portable or implantable pump is well known.
There are currently commercially available needle-like continuous measurement sensors, such as the Guardian & CGMS system of Medtronic company and another of Dexcom, and prior art US 2008/161666 to Feldman, U.S. Pat. No. 7,354,420 to Stell, U.S. Pat. No. 7,136,689 to Shults, but with a large error margin and a need for frequent calibration, 3-4 times daily with strips using a drop of blood (such as One Touch Ultra of LifeS-can Inc) by piercing of the finger.
Patents and patent applications such as Burton US 2003/0143746, Arvind US 2008/0234562, Korf U.S. Pat. No. 6,013,029, Lu Wang US 2007/0163894, disclose methods of self calibration, which are excellent for a large supply of glucose such as intravenously, but unsuitable for accurate interstitial measurements, where their use could result in a deficiency of the measured glucose due to the small available amount and to the small but substantial microdilution via dialysis. Additionally, the microdilution measurements are delayed, and their accuracy depends on the accuracy of the flow rate of the circulating liquid and the stability of the temperature.
In the patent application Nanostructured composite material and biosensor containing same GR2008100409 (Chaniotakis), an enhanced form sensor which has a long life-span against in vivo erosion is presented, although it lacks self calibration, which is essential for the reliability of closed-loop injections—an autonomous robotic system.
The need for a fully implantable artificial pancreas with simultaneous glucose measurement and robotic insulin infusion is known, but the presently available technologies do not meet the need for a reliable, and longlasting accurate measurement.
In the continuous measurement with a needle-like sensor in the subcutaneous tissue, the measurement of glucose differs from that of blood with time-delay and a different standard. Algorithms that are known through the relevant literature have been developed using neural networks and other methods (Mougia-kakou, A. Prountzou, D. Iliopoulou, et al. Nikita, A. Vazeou, C. S. Bartsocas, “Neural Network based Glucose—Insulin Metabolism Models for Children with Type 1 Diabetes,” Engineering in Medicine and Biology Conference 2006 (EMBC '06), IEEE, New York City, USA, September 2006, & Mougia-kakou, K. Prountzou, et al. Nikita, “A Real Time Simulation Model of Glucose-Insulin Metabolism for Type 1 Diabetes Patients,” Engineering in Medicine and Biology Conference 2005 (EMBC '05), IEEE, Shanghai, China, September 2005) with which we can predict the blood glucose at the instant of the subcutaneous measurement and 30 minutes later.
Yellambalase et al presented at the IMTC 2006 (Instrumentation and Measurement Technology Conference, Sorrento, Italy 24-27 Apr. 2006) a needle-type biosensor system with fully automated operations, in which an oxidase-coupled amperometric sensor with an oxygen depleting/generating actuator is interfaced with an electrochemical instrument and a perfusion system.
Microfluidic capillary blood absorption lumens are known in the art, in strip type glucose sensors, see Cul US 2006/0175205, Karinka U.S. Pat. No. 6,863,800, Say US 2008/167543.
It is also known that glucose penetrates microporous nanostructures, such as a nanofiber matrix with embedded glucose oxidase receptor (GOX) and an overcoat of a biomimetically-composed matrix film of silicon oxide, see the patent application with the priority GR2008100409 (Chaniotakis).
It is an intention of the present invention to provide a method for a reliable, accurate measurement of biomedical parameters with self-calibration and the prediction of blood glucose for the timely information of the user and the medical assessment and for the automatic closed-loop insulin infusion.